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Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer

PHASE1PHASE2RECRUITING

This is a first in human, open-label, multi-center Phase 1 / 2 study to evaluate the safety, tolerability, and initial efficacy of AU-007 in patients with advanced solid tumors. AU-007 will be administered either as a monotherapy, or in combination with a single loading dose of aldesleukin, or with both AU-007 and aldesleukin given every 2 weeks (Q2w). Once the recommended phase 2 dose (RP2D) of AU-007 plus aldesleukin is determined, AU-007 plus aldesleukin will also be administered with avelumab.

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Study details:

This is a first in human, multicenter, open-label Phase 1-2 study evaluating the safety, tolerability, and initial efficacy of AU-007 with or without aldesleukin, in patients with unresectable locally advanced or metastatic cancer. Patients must either be ineligible for or have progressed on prior standard of care therapy. Part 1 consists of 3 escalation Arms, each starting with a single 1+2 escalation cohort followed by 3+3 escalation cohorts to define the RP2D or maximum tolerated dose (MTD).

The study begins in Arm A evaluating escalating doses of AU-007 (Q2w) in sequential escalation cohorts to define RP2D or MTD. In Arm B, AU-007 (Q2w) is evaluated in combination with a single dose of aldesleukin given with the first AU-007 dose. AU-007 is administered Q2w with an escalating single aldesleukin dose in sequential escalation cohorts.

In Arm C, AU-007 is evaluated in combination with aldesleukin, both given Q2w. AU-007 will be administered with an escalating dose of aldesleukin in each sequential Arm C escalation cohort. The Part 2 cohort expansion portion of the study consists of up to three expansion Arms evaluating the initial efficacy of the RP2D from corresponding dose escalation Arms A, B, and C in selected solid tumor types, prioritizing melanoma, renal cell cancer, and non-small cell lung cancer (NSCLC).

Other eligible cancers include but are not limited to head and neck squamous cell carcinoma, urothelial cancer, gastric or gastro-esophageal cancer, and ovarian cancer. Part 3 evaluates the safety of AU-007 in combination with aldesleukin and avelumab, followed by one expansion cohort, in NSCLC.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Measurable or non-measurable disease as per RECIST v1.1 criteria and documented by CT and/or MRI. In Cohort Expansion, patients with truly non-measurable only disease (e.g., ascites, pleural or pericardial effusion, organomegaly), are not eligible for enrollment

In Dose Escalation patients must have selected tumor types and have progressed after standard of care treatment, or be intolerant to treatment, or refused standard treatment

Part 2 includes but is not limited to: Renal cell cancer progressing during or following at least two approved therapeutic regimens (e.g., small molecule inhibitors, anti-PDx therapy)

Cutaneous melanoma that is either locally unresectable or metastatic: BRAF wild type: progressed after receiving PD-1 containing therapy with or without an anti-CTLA-4; BRAF mutation: patients who refused BRAF+MEK inhibitor

NSCLC: Unresectable locally advanced or metastatic PD-L1-positive (≥ 1%) NSCLC not harboring an activating EGFR mutation or ALK rearrangement and has progressed during or following treatment with an anti-PDx and platinum-based chemotherapy (unless ineligible for platinum therapy)

Part 3: NSCLC as described above

Female patients of childbearing potential must have a negative serum or urine pregnancy test performed within 72 hours prior to the initiation of study drug administration. Female patients of childbearing potential must be willing to use two forms of contraception throughout the study, starting with Screening through 60 days after the last dose of study drug. Abstinence is acceptable if this is the established and the preferred contraception method for the patient

Male patients with partners of childbearing potential must use barrier contraception from the time of consent through 60 days after discontinuation of study drug and must not donate sperm during this period. In addition, male patients should have their partners use contraception (as documented for female patients) for the same period of time

Patients who have previously received an immune checkpoint inhibitor (e.g., anti-PD-L1, anti-PD-1, anti-CTLA-4) prior to enrollment must have checkpoint inhibitor immune-related toxicity resolved to either Grade ≤ 1 or baseline (prior to the checkpoint inhibitor) to be eligible for enrollment. Patients who experienced previous checkpoint inhibitor-related hypothyroidism are eligible for the study regardless of grade resolution if well controlled on thyroid hormone replacement therapy

Symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet the following at the time of enrollment: No concurrent treatment for CNS disease (e.g., surgery, radiation, corticosteroids ≥ 10 mg prednisone/day or equivalent); No concurrent leptomeningeal disease or cord compression

Exclusion criteria

Patients with a history of known autoimmune disease with exceptions of Vitiligo, Psoriasis, atopic dermatitis, or other autoimmune skin condition not requiring systemic treatment, History of Graves' disease in patients now euthyroid for > 4 weeks, Hypothyroidism managed by thyroid hormone replacement, Alopecia, Arthritis managed without systemic therapy beyond oral nonsteroidal anti-inflammatory drugs

Major surgery or traumatic injury within 8 weeks before first dose of AU-007

Unhealed wounds from surgery or injury

Treatment with > 10 mg per day of prednisone (or equivalent) or other immune-suppressive drugs within the 7 days prior to the initiation of study drug. Steroids for topical, ophthalmic, inhaled, or nasal administration are allowed

Prior anti-cancer therapy before the planned start of AU-007 as follows: Not recovered to baseline from toxicity of prior systemic cancer therapy(ies). Not recovered from toxicity of radiotherapy. Concurrent use of hormones either to maintain castrate levels of testosterone in patients with castration-sensitive prostate cancer or for non-cancer-related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable. Bisphosphonates are permitted.

Patients who have experienced serious adverse events during prior IL-2 therapy (including but not limited to bowel perforation, gastrointestinal bleeding, arrythmias, myocardial infarction, repetitive seizures)

Inflammatory process that has not resolved for ≥ 4 weeks from the date of first study dose. Patients with chronic low-grade inflammatory processes such as radiation-induced pneumonitis are excluded regardless of duration

Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include non-melanoma locally advanced skin cancer, cervical carcinoma in situ, localized prostate cancer (Gleason score ≤ 7), resected melanoma in situ, or any malignancy considered to be indolent and never required therapy, with the exception of indolent lymphomas

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-04-04

Primary completion: 2025-08-31

Study completion finish: 2025-09-30

Study type

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT05267626

Intervention or treatment

DRUG: AU-007

DRUG: Aldesleukin

DRUG: Avelumab

Conditions

• Advanced Solid Tumor
• Metastatic Cancer

Condition: Advanced Solid Tumor, Metastatic Cancer
DRUG: AU-007 and other drugs
Bedford Park, South Australia, Australia and more
Sponsor: Aulos Bioscience, Inc.

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Find a site

Closest Location:

Southern Oncology Clinical Research Unit

Research sites nearby

Select from list below to view details:

Southern Oncology Clinical Research Unit
Bedford Park, South Australia, Australia
Monash Health
Clayton, Victoria, Australia
Peninsula & South Eastern Haematology and Oncology Group
Frankston, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: AU-007 Monotherapy AU-007 (Q2w) will be administered as a monotherapy sequential ascending doses with each Dose Escalation Cohort	DRUG: AU-007 Monoclonal Antibody Targeting IL-2
EXPERIMENTAL: AU-007 combined with an aldesleukin loading dose AU-007 (Q2w) will be administered in combination with a single dose of aldesleukin with the initial AU-007 dose.	DRUG: AU-007 Monoclonal Antibody Targeting IL-2
EXPERIMENTAL: AU-007 combined with aldesleukin given concomitantly AU-007 will be administered in combination with aldesleukin, both administered Q2w.	DRUG: AU-007 Monoclonal Antibody Targeting IL-2
EXPERIMENTAL: AU-007 combined with aldesleukin and avelumab given concomitantly AU-007 and avelumab will be administered Q2w, with either a single loading dose or Q2w aldesleukin.	DRUG: AU-007 Monoclonal Antibody Targeting IL-2

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Evaluate the safety and tolerability of AU-007	Measured by the frequency of DLTs (Dose limiting toxicity) and safety profile	Day 1 thru end of treatment (EOT) visit (28 days after last dose)
Establish the maximum tolerated dose (MTD) and/or RP2D	With AU-007 alone or in combination with aldesleukin measured by pharmacokinetics (PK), pharmacodynamics (PD), and Biomarkers	Day 1 thru EOT visit (28 days after last dose)

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Magnitude of PK changes in the blood after dosing determined by area under the curve (AUC) of AU-007	The AUC of AU-007 will be measured at different timepoints after AU-007 administration	Day 1 thru EOT visit (28 days after last dose)
Magnitude of PK changes in the blood after dosing determined by maximum concentration (Cmax) of AU-007	The Cmax of AU-007 will be measured at different timepoints after AU-007 administration	Day 1 thru EOT visit (28 days after last dose)
Magnitude of PK changes in the blood after dosing determined by time of maximum concentration (Tmax)	The Tmax of AU-007 will be measured at different timepoints after AU-007 administration	Day 1 thru EOT visit (28 days after last dose)
Magnitude of PK changes in the blood after dosing determined by Half-life (T1/2) of AU-007	The T1/2 of AU-007 will be measured at different timepoints after AU-007 administration	Day 1 thru EOT visit (28 days after last dose)
Magnitude of cytokine changes in the blood after dosing	Not Specified	Day 1 thru EOT visit (28 days after last dose)
Magnitude of immunogenicity after dosing with AU-007 alone or in combination with aldesleukin	Assessed by summarizing the number of patients who develop detectable anti-drug antibodies (ADAs) at different timepoints after AU-007 alone or in combination with aldesleukin	Day 1 thru EOT visit (28 days after last dose)
Evaluate the preliminary anti-tumor activity of AU-007 alone, in combination with aldesleukin, and in combination with aldesleukin and avelumab in patients with unresectable locally advanced or metastatic cancer	Clinical anti-tumor activity will be evaluated using conventional Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and modified RECIST v1.1.	Day 1 thru EOT visit (28 days after last dose)

Frequently Asked Questions

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References

Clinical Trials Gov: Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer